Perinatal Hypophosphatasia: Tissue Levels of Vitamin B6 Are Unremarkable Despite Markedly Increased Circulating Concentrations of Pyridoxal-5'-phosphate. Evidence for an Ectoenzyme Role for Tissue-nonspecific Alkaline Phosphatase

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1988 Apr 1

PMID 3350970

Citations 32

Authors

M P Whyte

J D Mahuren

K N Fedde

F S Cole

E R McCabe

S P Coburn

Affiliations

Soon will be listed here.

Abstract

"Perinatal" hypophosphatasia is the most severe form of this inborn error of metabolism, which is characterized by deficient activity of the tissue-nonspecific (liver/bone/kidney) isoenzyme of alkaline phosphatase (ALP) (TNSALP). We report that autopsy tissue from three affected subjects, which was profoundly low in ALP activity, had essentially unremarkable levels of pyridoxal-5'-phosphate (PLP), pyridoxal, and total vitamin B6 content despite markedly elevated plasma PLP levels (5,800, 14,500, and 98,500 nM; adult norm, 5-109 nM). Our findings help to explain the general absence of symptoms of vitamin B6 excess or deficiency in hypophosphatasia, and provide evidence that TNSALP acts as an ectoenzyme to regulate extracellular rather than intracellular concentrations of PLP (the cofactor form of vitamin B6) and perhaps other phosphate compounds.

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References

DANOVITCH S, BAER P, LASTER L . Intestinal alkaline phosphatase activity in familial hypophosphatasia. N Engl J Med. 1968; 278(23):1253-60. DOI: 10.1056/NEJM196806062782303. View

Low M, Saltiel A . Structural and functional roles of glycosyl-phosphatidylinositol in membranes. Science. 1988; 239(4837):268-75. DOI: 10.1126/science.3276003. View

Potera C, Rose D, Brown R . Vitamin B6 deficiency in cancer patients. Am J Clin Nutr. 1977; 30(10):1677-9. DOI: 10.1093/ajcn/30.10.1677. View

Coleman R, Schofield B, McDONALD D . Selective localization of a Golgi apparatus acid phosphatase isoenzyme in bone using pyridoxal-5'-phosphate. J Histochem Cytochem. 1980; 28(2):115-23. DOI: 10.1177/28.2.7354210. View

Anderson B, OBrien H, Griffin G, MOLLIN D . Hydrolysis of pyridoxal-5'-phosphate in plasma in conditions with raised alkaline phosphate. Gut. 1980; 21(3):192-4. PMC: 1420355. DOI: 10.1136/gut.21.3.192. View

Low M, ZILVERSMIT D . Role of phosphatidylinositol in attachment of alkaline phosphatase to membranes. Biochemistry. 1980; 19(17):3913-8. DOI: 10.1021/bi00558a004. View

Labarca C, Paigen K . A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980; 102(2):344-52. DOI: 10.1016/0003-2697(80)90165-7. View

Kyaw A . A nuclear phosphatase that specifically hydrolyzes pyridoxal 5'-phosphate in mouse liver. Biochem Med. 1980; 24(1):27-32. DOI: 10.1016/0006-2944(80)90083-6. View

Fallon M, Whyte M, Teitelbaum S . Stereospecific inhibition of alkaline phosphatase by L-tetramisole prevents in vitro cartilage calcification. Lab Invest. 1980; 43(6):489-94. View

10.

Shideler C . Vitamin B6: an overview. Am J Med Technol. 1983; 49(1):17-22. View

11.

Coburn S, Mahuren J . A versatile cation-exchange procedure of measuring the seven major forms of vitamin B6 in biological samples. Anal Biochem. 1983; 129(2):310-7. DOI: 10.1016/0003-2697(83)90555-9. View

12.

Wilson P, Smith G, Peters T . Pyridoxal 5'-phosphate: a possible physiological substrate for alkaline phosphatase in human neutrophils. Histochem J. 1983; 15(3):257-64. DOI: 10.1007/BF01006240. View

13.

MUELLER H, Stinson R, Mohyuddin F, Milne J . Isoenzymes of alkaline phosphatase in infantile hypophosphatasia. J Lab Clin Med. 1983; 102(1):24-30. View

14.

Schaumburg H, Kaplan J, Windebank A, Vick N, Rasmus S, Pleasure D . Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med. 1983; 309(8):445-8. DOI: 10.1056/NEJM198308253090801. View

15.

Lumeng L, Schenker S, Li T, Brashear R, Compton M . Clearance and metabolism of plasma pyridoxal 5'-phosphate in the dog. J Lab Clin Med. 1984; 103(1):59-69. View

16.

Merrill Jr A, Henderson J, Wang E, McDonald B, Millikan W . Metabolism of vitamin B-6 by human liver. J Nutr. 1984; 114(9):1664-74. DOI: 10.1093/jn/114.9.1664. View

17.

Whyte M, McALISTER W, Patton L, Magill H, Fallon M, Lorentz Jr W . Enzyme replacement therapy for infantile hypophosphatasia attempted by intravenous infusions of alkaline phosphatase-rich Paget plasma: results in three additional patients. J Pediatr. 1984; 105(6):926-33. DOI: 10.1016/s0022-3476(84)80079-7. View

18.

MUELLER H, Leung H, Stinson R . Different genes code for alkaline phosphatases from human fetal and adult intestine. Biochem Biophys Res Commun. 1985; 126(1):427-33. DOI: 10.1016/0006-291x(85)90623-0. View

19.

Whyte M, Mahuren J, Vrabel L, Coburn S . Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism. J Clin Invest. 1985; 76(2):752-6. PMC: 423894. DOI: 10.1172/JCI112031. View

20.

Whyte M, Magill H, Fallon M, Herrod H . Infantile hypophosphatasia: normalization of circulating bone alkaline phosphatase activity followed by skeletal remineralization. Evidence for an intact structural gene for tissue nonspecific alkaline phosphatase. J Pediatr. 1986; 108(1):82-8. DOI: 10.1016/s0022-3476(86)80773-9. View